MicroRNA 143-145 deficiency impairs vascular function
MetadataShow full item record
MicroRNAs are required for vascular smooth muscle growth, differentiation and function. MiR143-145 modulates cytoskeletal dynamics and acquisition of the contractile phenotype by smooth muscle cells. Lack of this miRNA cluster results in decreased blood pressure and reduced vasocontraction. As all these observations point to a key role for miR143-145 in the vasculature, we investigated whether miR143-145 deficiency is associated with impaired vascular tone. Vasocontraction was assessed in isolated aortic rings from miR143-145 KO and wild type animals incubated with increasing concentrations of phenylephrine (10 -9 M to 10 -5 M) or KCI 0.3M. In both cases, aortic vessel contraction was dramatically reduced in miR143-145 KO animals compared to controls. Next, aortic rings were pre-contracted with phenylephrine (EC60: 10 -7 M) and concentration responses for acetylcholine were obtained. A significantly reduced vasodilation was observed in miR143-145 KO animals compared to controls and similar results were obtained when an exogenous donor of nitric oxide (sodium nitroprusside) was used. Endothelial nitric oxide synthase or guanylate cyclase mRNA expression were not different between the animal groups thus suggesting to investigate the effect of other vasodilators. Isoprenaline mediated vasodilation was significantly reduced in miR143-145 KO animals compared to controls in the absence or in the presence of the guanylate cyclase inhibitor ODQ (10 -4 M), suggesting that also beta adrenergic vasodilation is impaired following miR143-145 deficiency. Finally, the effect of a stable mimetic prostacyclin, namely iloprost, was investigated and again a reduced vasodilation was observed in miR143-145 KO animals. MiR143-145 deficiency is associated not only with altered vasocontraction but also with impaired vasodilation, which probably reflects the impaired VSMC differentiation phenotype reported in miR143-145 KO animals. Copyright © by BIOLIFE, s.a.s.
Showing items related by title, author, creator and subject.
Hodgson, J.; Woodman, R.; Croft, K.; Ward, Natalie; Bondonno, C.; Puddey, I.; Lukoshkova, E.; Head, G. (2014)Background: Characteristics of short-term blood pressure (BP) variation may influence cardiovascular disease risk via effects on vascular function. Objective: In a cross-sectional study of a group of treated hypertensive ...
Choroid plexus dysfunction: The initial event in the pathogenesis of Wernicke's encephalopathy and ethanol intoxicationNixon, P.; Jordan, L.; Zimitat, Craig; Rose, S.; Zelaya, F. (2008)Background: In both acute ethanol intoxication and in thiamin deficient glucose metabolism, previous studies have detected blood-brain barrier (BBB) and/or blood-CSF-barrier (BCSFB) impairment but were unable to assess ...
Alaei Shahmiri, Fariba (2012)Chronic diseases, such as cardiovascular disease and diabetes, are the leading causes of morbidity and mortality worldwide. Recent studies have shown that in addition to diabetes mellitus, non-diabetic degrees of fasting ...